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David A. Dean, Ph.D.

Contact Information

Phone Numbers

Administrative: (585) 275-5948

Office: (585) 276-3933

Office: (585) 756-7780

Research Labs

Lab: (585) 275-3577

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Biography

Research

Despite all of the hype regarding gene therapy, at present, gene therapy is a dream due to insufficient levels of gene transfer and expression at desired sites. One way to increase gene expression is to target more DNA to the cell nucleus. Since the nucleus is the site of transcription, without the movement of plasmids through the cytoplasm, translocation into the nucleus, and localization to the appropriate subnuclear domain, no gene expression, or "gene therapy" can take place. Ongoing projects in my laboratory are studying the mechanisms of cytoplasmic trafficking of plasmids along the cytoskeleton, plasmid nuclear entry, subnuclear organization, and exploiting what we learn to improve gene therapy.


We have shown that plasmids are able to enter the nucleus in a sequence-specific manner that appears to be mediated by transcription factor binding. My lab is interested in identifying the proteins required for this activity and the regulation of their nuclear import. Based on our model, we have created cell-specific plasmids by incorporating DNA sequences that bind to cell-specific transcription factors. At present, we have examples of smooth muscle, alveolar epithelial cell, and endothelial cell-targeting vectors that we hope to use for the treatment of a number of pulmonary diseases, and we are working to expand our repertoire to selectively target expression to any desired cell or tissue.


We also are developing methods for extracellular delivery of non-viral vectors in animal models for disease. Using electroporation, we have obtained very high levels of gene expression in the vasculature and lungs of animals. We have used this approach to prevent and/or cure existing disease in models of acute lung injury and asthma in mice and rats. Our next goal is to optimize these approaches in more relevant preclinical models to move toward clinical application.

Credentials

Faculty Appointments

Specialties

  • Neurological Surgery - American Board of Neurological Surgery

Education

1985
BA | University of California at San Diego
Biochemistry

1990
PhD | University of California at Berkeley
Microbiology

Post-doctoral Training & Residency

07/01/1967 - 01/01/1968
Residency in Surgery-General at Wilford Hall Medical Center (AETC)

07/01/1965 - 06/30/1966
Internship in Surgery-General at Tulane Medical Center Office of Graduate Medical Education

01/01/1968 - 12/31/1971
Residency in Neurological Surgery at Wilford Hall Medical Center (AETC)

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Awards

2011
Ruth A. Lawrence Academic Faculty Service Award in Research
Location: University of Rochester

2006
Mentoring the Mentors
Sponsor: Searle Center for Teaching Excellence
Location: Northwestern University

2005
Sandler Program for Asthma Research Senior Investigator
Sponsor: unsolicited conversion of award status
Location: Northwestern University

1991 - 1994
NIH Individual Postdoctoral Fellowship (NRSA)

1984
Presdents Undergraduate Scholarship
Location: University of California

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Publications

Journal Articles

7/2017
Barnett RC, Lin X, Barravecchia M, Norman RA, de Mesy Bentley KL, Fazal F, Young JL, Dean DA. "Featured Article: Electroporation-mediated gene delivery of surfactant protein B (SP-B) restores expression and improves survival in mouse model of SP-B deficiency." Experimental biology and medicine. 2017 Jul 0; 242(13):1345-1354. Epub 2017 Jun 05.

6/24/2017
Rahmani K, Dean DA. "Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1)." Biochemical and biophysical research communications.. 2017 Jun 24; 488(2):253-258. Epub 2017 Apr 12.

12/2016
Parikh P, Bai H, Swartz MF, Alfieris GM, Dean DA. "Identification of differentially regulated genes in human patent ductus arteriosus." Experimental biology and medicine. 2016 Dec 0; 241(18):2112-2118. Epub 2016 Jul 28.

Books & Chapters

2013
Chapter Title: Extracellular and Intracellular Barriers to Non-Viral Gene Transfer
Book Title: Novel Gene Therapy Approaches
Author List: Gottfried, L., and D. A. Dean
Edited By: M. Wei and D. Good
Published By: Intech Press2013 in Rijecka, Croatia

2013
Chapter Title: Electroporation-mediated Gene Delivery to the Lungs
Book Title: Electroporation Protocols: Experimental and Clinical Medicine
Author List: Young, J. L., M. Barravecchia, and D. A. Dean
Edited By: S. Li
Published By: Humana Press2013 in Totowa, NJ

2010
Chapter Title: Nonviral gene delivery
Book Title: Optical Imaging Techniques: A Laboratory Manua
Author List: Dean, D. A., and J. Z. Gasiorowski
Edited By: R. Yuste, F. Lanni, and A. Konnerth
Published By: Cold Spring Harbor Laboratory Press2010 in Cold Spring Harbor, NY

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